For decades, guinea worm disease, caused by the parasitic worm Dracunculus medinensis, has been a major public health concern, impacting vulnerable populations in Africa and Asia. This review gives an in-depth examination of the various therapeutic approaches used to combat guinea worm disease. This study seeks to provide a current and evidence-based summary of available treatment techniques by conducting an exhaustive examination of peer-reviewed literature, medical databases, and official health organisation publications. The current review intends to contribute to the knowledge base and influence plans for guinea worm disease control and eradication by critically evaluating the success and obstacles associated with various treatment approaches through standard heterocyclic medications, herbal sources, phytochemicals, and nanomedicines. The importance of integrating community engagement and collaboration among national and international stakeholders is emphasised to foster sustainable solutions and ensure a collective effort towards a guinea worm-free world.